Chapter 68
GINGER
(Zingiber officinale Roscoe)
HISTORY
Ginger has been a part of traditional Chinese medicine
at least since the 4th century BC, particularly for hepatic
and other gastrointestinal disorders.1 Two millennia
before the birth of Christ, the Vedic literature of India
included information on the use of ginger as a spice and
an herb; Marco Polo also documented the use of ginger
in India during the 13th century. The ancient Greeks and
Romans used ginger as a spice. Traditional Arabian
medicine used ginger for treating constipation, colds,
bronchitis, cataracts, and stomach acidity.
BOTANICAL DESCRIPTION
Common Name: Ginger, Jiang [Chinese], Gingem-
bre [French], Ingwer [German], Zenzero [Italian],
Shoga [Japanese], Gengibre [Portuguese],
Jengibre [Spanish]
Scientific Name: Zingiber officinale Roscoe
Botanical Family: Zingiberaceae (ginger family)
Physical Description: This slender, perennial herb
has upright stems and narrow medium green
leaves arranged in two ranks on each stem. Ginger
reaches up to 1.5 m (5 ft) in height with leaves
about 2 cm (0.8 in.) wide and 20 cm (8 in.) long.
This plant grows from a thick, aromatic under-
ground stem (rhizome), which has a branched,
uneven (warty) surface. The inflorescence forms a
dense spike up to 8 cm (3 in.) tall on a different
stem than the leaves. The bracts are green with
translucent margins and the small flowers are
Medical Toxicology of Natural Substances, by Donald G. Barceloux, MD
Copyright 2008 John Wiley & Sons, Inc.
482
yellow-green with purple lips and cream-colored
blotches. The fruiting body is a triangular-oval
capsule containing many irregular, black seeds.
Distribution and Ecology: Ginger is indigenous to
the warm, humid, shady tropical parts of southern
Asia, but now this plant is cultivated commercially
in Jamaica, West Indies, Haiti, China, and Nigeria.
Harvest occurs about 56 months after planting
fresh ginger and 89 months after planting dry
ginger. Major producers of dry ginger include
India, China, Taiwan, Sierra Leone, Nigeria,
Jamaica, Fiji, and Australia.2
EXPOSURE
Sources
Ginger is a spice, flavoring agent, and herbal medicine
used as both fresh and dried preparations of the ginger
rhizomes. The rhizome is the plant part used for culinary
as well as medicinal purposes. Some reduction in the
major constituents (i.e., gingerols) occurs during the
commercial drying process as a result of the dehydra-
tion of gingerols to shogaols.3 The main source of ginger
is the root and rhizome of Zingiber officinale. Ginger
and ginger extracts are common constituents of foods
and beverages including chutney, pickles, liquors, and
bakery products. Common medicinal forms of ginger
include fresh root, dried root, tablets, capsules (50
550 mg), liquid extract, tincture, and teas. Ginger oil
is a steam distillate of fresh ginger rhizome or
powdered ginger composed primarily of sesquiterpene

hydrocarbons (e.g., zingiberene).2 Whole, intact rhi-
zomes are the best source of the essential oil of ginger
because of the presence of substantial amounts of the
oil in the peel. Whole dried ginger has a loose corky
layer; peeled ginger has a line of fiber bundles exposed
by removal of the cork layer. Although there is no uni-
versal standard, ginger products are often standardized
to gingerol content.
Medicinal Uses
Traditional
Traditional medicine in China, Japan, and India use the
rhizomes and stems of ginger as a component of the
herbal treatment of digestive disorders (indigestion,
flatulence, constipation, nausea), headaches, rheuma-
tism, colds, and cough. A large portion of traditional
Chinese herbal remedies contain ginger. In the Ayurvedic
medical practice in India, ginger is an herbal treatment
for colds and other viral infections, poor appetite, diges-
tive problems, arthritis, and headache.4,5
Current
Current medicinal uses of ginger include motion sick-
ness, nausea and vomiting (postsurgical, pregnancy, che-
motherapy-induced), and osteoarthritis. Ginger is one
of the most common herbal treatments for nausea and
vomiting in pregnancy along with chamomile, pepper-
mint, and raspberry leaf. There is supportive evidence
from a randomized controlled trial and an open-label
study that ginger reduces the severity and duration of
chemotherapy-induced nausea and vomiting.6 The addi-
tion of ginger to a standard antiemetic regimen proba-
bly does not reduce the nausea or vomiting associated
with chemotherapy.7 Limited evidence supports the use
of ginger for the reduction of nausea and vomiting asso-
ciated with pregnancy, motion sickness, and surgery.8
Most of the limited number of randomized clinical trials
of ginger for the treatment of nausea and vomiting of
early pregnancy demonstrate positive results, but these
studies involve only several hundred patients and larger
trials are necessary to determine the efficacy and safety
of ginger relative to other treatments.9 A randomized,
controlled equivalence trial involving 291 pregnant
women (<16 weeks gestation) administered daily doses
of 1.05 g ginger capsules or 75 mg vitamin B6 did not
detect a statistically significant difference between the
two treatment groups as measured by the Rhodes index
of nausea and vomiting scale.10 There was no placebo
group. No clinical trials of ginger for the treatment for
hyperemesis gravidarum show consistent, long-term
benefit.11
68 GINGER
In a randomized, double-blinded trial involving 180
patients undergoing gynecologic laparoscopy, ginger did
not reduce the incidence of postoperative nausea and
vomiting after these procedures.12 In a study of 28 vol-
unteers, the administration of powdered ginger (whole
root, 0.5 g or 1.0 g) or fresh ginger root (1 g) provided
no protection against the motion sickness caused by a
rotating chair.13 Additionally, the administration of
ginger did not significantly alter gastric function during
motion sickness.
Regulatory Status
The German Commission E approves the use of ginger
for dyspepsia, nausea and vomiting of pregnancy, and
for prophylaxis of motion sickness. Ginger is listed on
the General Sale List of the Medicines Control Agency
of the United Kingdom. In the United States, ginger is
a dietary supplement that is listed as generally recog-
nized as safe (GRAS).
PRINCIPAL INGREDIENTS
Chemical Composition
The major pungent compounds in ginger are gingerols,
particularly 6-gingerol. Other gingerols include
8-gingerol, 10-gingerol, methylgingerol, gingerdiol,
dehydrogingerdione, gingerdiones, diarylheptanoids
(curcuminoids), diterpene lactones, and galanolactone.14
Gingerols are thermally unstable, and dehydrate (i.e.,
loss of hydroxyl group from C5 and a hydrogen from
C4 with the formation of double bond between C4 and
C5) to the corresponding shogaol compounds. Figure
68.1 displays the chemical structures of the major gin-
gerol and shogaol compounds in ginger. Fresh ginger
rarely contains zingerone and shogaols depending on
the variety or cultivars, but the concentrations of these
compounds increase significantly in dried preparations
of ginger. Shogaol compounds also occur naturally in
dried ginger along with vanillin, dihydroferulic acid,
ferulic acid, and zingerone. Figure 68.2 displays the
transformation of gingerols to zingerone, shogaols,
and paradols.
In samples of fresh Australian ginger, 6-gingerol was
the major pungent phenolic compound, while 8-gingerol
and 10-gingerol were present in lower concentrations.15
The mean concentration of these three gingerol com-
pounds in fresh ginger rhizomes were 215 54 g/g, 75
31 g/g, and 73 26 g/g, respectively. This study did
not detect shogaol compounds in the ethanol extracts
from fresh rhizomes, as measured by high performance
liquid chromatography with UV detection (HPLC/UV).
Analysis of fresh Hawaiian white and yellow ginger and
483
PART 3 MEDICINAL HERBS and ESSENTIAL OILS

a methylene chloride extract of commercially processed
dry ginger by HPLC detected 115 compounds.16 In addi-
tion to gingerol and shogaol compounds, other constitu-
ents included paradols (5-deoxygingerols), isogingerols,
isoshogaols, gingerdiones, methoxy-gingerols, mono-
and di-acetoxy-gingerdiols, dihydro-paradols, diaryl-
heptanoids, 4-vinylguaiacol, acetovanillone, and some
methyl ether derivatives.
Ginger contains about 13.5% essential oil following
steam distillation.2 This product contains relative high
concentrations of sesquiterpene hydrocarbons (e.g.,
zingiberene), relatively small amounts of monoterpene
hydrocarbons, and oxygenated compounds compared
with dry ginger. There are a variety of compounds (e.g.,
camphene, -phellandrene, -bisabolene, -farnesene)
in the essential oil depending on the extraction process,
O OH
H3CO
(CH2)n
[6]-gingerol, n = 4
HO [8]-gingerol, n = 6
[10]-gingerol, n = 8
O pounds (e.g., 8-gingerol, 10-gingerol). However, shogaol
H3CO
(CH2)n
[6]-shogaol, n = 4
HO [8]-shogaol, n = 6
[10]-shogaol, n = 8
FIGURE 68.1. Chemical structures of major gingerol and
shogaol compounds in ginger.
strain, and the source (dried, fresh). The main sesquiter-
pene hydrocarbons in ginger oil prepared from fresh
ginger rhizomes were -zingiberene (2730%), -
curcumene (89%), -sesquiphellandrene (4.8%), and
bisabolene (3.2%) as measured by gas chromatography/
mass spectrometry (GC/MS).17 Minor constituents of
the essential oil of ginger include acyclic -farnesene
and a variety of monoterpene compounds (limonene,
myrcene, -pinene, borneol, citronellol, geraniol, lin-
alool).14 Deterioration of ginger root may cause the for-
mation of mycotoxins (e.g., mycophenolic acid) from
the degradation of the root by fungi (e.g., Penicillium
brevicompactum).18 Currently, there is no evidence that
the formation of mycophenolic acid in ginger causes
human disease.
Physiochemical Properties
Gingerols exhibit novel reversible kinetics as a result
CH3 of dehydrationhydration transformations with corre-
sponding shogaols. The dehydration of gingerol is pH
and temperature dependent with 6-gingerol being rela-
tively stable at pH 4. The degradation of 6-gingerol is
complete within 2 hours at pH 1 and 100 C (212 F).19
6-Gingerol is more pungent than other gingerol com-
CH3
compounds are more pungent and lipophilic than cor-
responding gingerol compounds. In vitro studies suggest
that gingerol inhibits thromboxane B2 and prostaglan-
din D2 formation by arachidonic acid.20 However, the
effect of dried ginger on thromboxane synthetase
activity is dose-dependent, and up to 2 g dried ginger
probably does not cause clinically significant platelet

O OH O
H3CO CH3 H3CO
(CH2)n Retro-Aldol CH3
[6]-gingerol, n = 4 Zingerone
HO i. Pyrolysis, 200C
[8]-gingerol, n = 6 HO
ii. 5% Ba(OH)2; Heat
[10]-gingerol, n = 8 + OHC(CH2)n CH3
Hexanal, n = 4
Dehydration Octanal, n = 6
pH 2.57.2
Decanal, n = 8
Heat

O O
H3CO CH3 H3CO
(CH2)n CH3
(CH2)n
[6]-shogaol, n = 4 Paradols
HO [8]-shogaol, n = 6 HO
[6]-paradol, n = 4
[10]-shogaol, n = 8
[8]-paradol, n = 6
[10]-paradol, n = 8

FIGURE 68.2. Transformation of gingerols. Adapted from Afzal M, et al. Ginger: an ethnomedical, chemical and pharmacolog-
ical review. Drug Metab Drug Interact 2001;18:164.

484

dysfunction.21 In a study of patients with coronary artery
disease, the administration of 4 g powdered ginger daily
for 3 months did not affect ADP- and epinephrine-
induced platelet aggregation, fibrinolytic activity, or
plasma fibrinogen concentration.22 However, a single
dose of 10 g powdered ginger administered produced a
significant reduction in platelet aggregation induced by
the ADP and epinephrine. In vitro studies suggest that
ginger may produce anti-inflammatory effects by inhib-
iting arachidonic acid metabolism, cyclooxygenase, and
lipoxygenase pathways.23 In vitro studies also indicate
that gingerol compounds are novel capsaicin-activated
VR1 (vanilloid) receptor agonists.24
Mechanism of Toxicity
Potential active antiemetic agents in the rhizome of
ginger include shogaol and gingerol. Some of the anti-
emetic activity may result from the presence of gin-
gerols, 6-shogaol, and galanolactone, which inhibit 5-HT3
receptor function. In vitro studies indicate that these
compounds are not competitive antagonists at the 5-
HT3 receptor, and the anti-emetic effect probably results
from the binding of these compounds to a modulatory
site distinct from serotonin.25
DOSE RESPONSE
The typical daily dose of fresh ginger is about 24 g
(1.0 in./2.5 cm rhizome) or 0.51.0 g powdered dry
rhizome in 34 divided doses. There are few data on the
toxicity of ginger following the ingestion of doses of
ginger exceeding typical therapeutic amounts. A clinical
trial used a single dose of 10 g powdered ginger admin-
istered to patients with coronary artery disease, but the
study did not report adverse effects.22
TOXICOKINETICS
Absorption
Based on in vitro studies, the dehydrated product (i.e.,
shogaol) undergoes almost complete reversion to
gingerol in the acidic conditions of the stomach at
body temperature (37.0 C/98.6 F).19 Consequently, the
dehydration of gingerol to shogaol may not reduce the
bioavailability of gingerol.
Biotransformation
In rats, 6-gingerol undergoes conjugation, -1 oxidation
and -oxidation at the phenolic side chain.26 The bile
contains about 48% of an orally administered dose of
6-gingerol for over 60 hours, whereas about 12% appears
68 GINGER
in the urine as multiple metabolites (e.g., vanillic acid,
ferulic acid, 9-OH-6-gingerol) and (S)-(+)-6-gingerol.
There are few pharmacokinetic data on gingerol in
humans.
Drug Interactions
Theoretically, ginger may increase the risk of bleeding
when ingested with other drugs or herbs that affect
coagulation. Because ginger can inhibit thromboxane
formation and platelet aggregation, concomitant use
with anticoagulants is not usually recommended.
However, there is no clear evidence that these potential
effects are clinically relevant. In an open-label, three-
way crossover study of 12 healthy volunteers receiving
pretreatment for 7 days with standard doses of ginger,
there was no significant effect on clotting parameters or
the pharmacokinetics of warfarin.27 Outcomes included
measurement of platelet aggregation, international nor-
malized ratio (INR), warfarin protein binding, plasma
warfarin concentrations, and S-7-hydroxywarfarin con-
centrations in the urine. A case report of a 76-year-old
woman on long-term phenprocoumon therapy associ-
ated the development of an elevated INR (>10) and
epistaxis with the use of ginger and tea from ginger
powder.28 Prior to the use of ginger, she had a stable
INR, and her INR returned to the normal therapeutic
range at the same phenprocoumon dose after cessation
of ginger use. Other potential drug interactions include
an increased effect of hypoglycemics and antihyperten-
sive agents, and decreased efficacy of histamine2-
blockers (e.g., ranitidine) and proton-pump inhibitors
(e.g., lansoprazole).
CLINICAL RESPONSE
There are few reports of toxicity associated with the use
of ginger. Exposure to ginger is one of the most common
contact allergens among spices based on patch testing.29
Consumption of excessive amounts of ginger may cause
sedation. Adverse effects of ginger during clinical trials
include headache, diarrhea, abdominal discomfort,
esophageal reflux, and drowsiness.30 Although the
number of subjects was limited, follow-up of random-
ized clinical trails on the use of ginger during pregnancy
did not demonstrate an increased incidence of sponta-
neous abortions, stillbirths, neonatal deaths, low birth
weight, or congenital abnormalities, when compared
with the placebo group.31,32 Ginger Jake paralysis was a
peripheral neuropathy that was associated with the con-
sumption of an alcoholic ginger extract, Jamaica ginger.
This neurological condition resulted from contamina-
tion of this beverage with triorthocresyl phosphate
rather than any constituent in ginger.
485
PART 3 MEDICINAL HERBS and ESSENTIAL OILS
DIAGNOSTIC TESTING
The combination of high performance liquid chroma-
tography (HPLC) with UV photodiode array detection
and electrospray mass spectrometry allows the detec-
tion of constituents of ginger and ginger extracts. HPLC
with mass spectrometry or nuclear magnetic resonance
spectroscopy provides rapid determination of ginger
constituents without sample purification or synthetic
standards.33 Thermal degradation and dehydration of
gingerol compounds can occur during gas chromato-
graphic analysis, resulting in the formation of aliphatic
aldehydes, zingerones, and the corresponding shogaol
compounds. Liquid chromatography/electrospray
ionization/tandem mass spectrometry coupled with
diode array detection identification is an alternative to
GC/MS for the analysis of gingerol-related compounds,
especially for thermally labile constituents.34 At least
during short-term storage, gingerol and shogaol are
relatively stable at room temperature in the absence
of strong acids or bases.19 Aged essential oil of ginger
contains relatively high amounts of -curcumene and
smaller amounts of zingiberene.2
TREATMENT
There are few data on the toxicity associated with exces-
sive amounts of ginger. Treatment is supportive.
References
1. Afzal M, Al-Hadidi D, Menon M, Pesek J, Dhami MS.
Ginger: an ethnomedical, chemical and pharmacological
review. Drug Metab Drug Interact 18:159190.
2. Govindarajan VS. Gingerchemistry, technology, and
quality evaluation: part 1. Crit Rev Food Sci Nutr 1982;17:
196.
3. Joland SD, Lantz RC, Solyom AM, Chen GJ, Bates RB,
Timmermann BN. Fresh organically grown ginger
(Zingiber officinale): composition and effects on LPS-
induced PGE2 production. Phytochemistry 2004;65:
19371954.
4. Mustafa T, Srivastava KC. Ginger (Zingiber officinale) in
migraine headache. J Ethnopharmacol 1990;29:267273.
5. Ghayur MN, Gilani AH. Pharmacological basis for the
medicinal use of ginger in gastrointestinal disorders. Dig
Dis Sci 2005;50:18891897.
6. Ernst E, Pittler MH. Efficacy of ginger for nausea and
vomiting: a systematic review of randomized clinical trials.
Br J Anaesth 2000;84:367371.
7. Manusirivithaya S, Sripramote M, Tangjitgamol S,
Sheanakul C, Leelahakorn S, Thavaramara T,
Tangcharoenpanich K. Antiemetic effect of ginger in
486
gynecologic oncology patients receiving cisplatin. Int J
Gynecol Cancer 2004;14:10631069.
8. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S,
Leeprakobboon K, Leelasettagool C. The efficacy of
ginger for the prevention of postoperative nausea and
vomiting: a meta-analysis. Am J Obstet Gynecol 2006;194:
9599.
9. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA.
Effectiveness and safety of ginger in the treatment of
pregnancy-induced nausea and vomiting. Obstet Gynecol
2005;105:849856.
10. Smith C, Crowther C, Willson K, Hotham N, McMillian V.
A randomized controlled trial of ginger to treat nausea
and vomiting in pregnancy. Obstet Gynecol 2004;103:
639645.
11. Jewell D, Young G. Interventions for nausea and vomiting
in early pregnancy. Cochrane Database Syst Rev
2003;(4):CD000145.
12. Eberhart LH, Mayer R, Betz O, Tsolakidis S, Hilpert W,
Morin AM, et al. Ginger does not prevent postoperative
nausea and vomiting after laparoscopic surgery. Anesth
Analg 2003;96:995998.
13. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of
ginger on motion sickness susceptibility and gastric func-
tion. Pharmacology 1991;42:111120.
14. Chrubasik S, Pittler MH, Roufogalis BD. Zingiberis
rhizoma: a comprehensive review on the ginger effect and
efficacy profiles. Phytomedicine 2005;12:684701.
15. Wohlmuth H, Leach DN, Smith MK, Myers SP. Gingerol
content of diploid and tetraploid clones of ginger (Zingiber
officinale Roscoe). J Agric Food Chem. 2005;53;
57725778.
16. Jolad SD, Lantz RC, Chen GJ, Bates RB, Timmermann
BN. Commercially processed dry ginger (Zingiber offici-
nale): composition and effects on LPS-stimulated PGE2
production. Phytochemistry 2005;66:16141635.
17. Antonious GF, Kochhar TS. Zingiberene and curcumene
in wild tomato. J Environ Sci Health B 2003;38:489
500.
18. Overy DP, Frisvad JC. Mycotoxin production and posthar-
vest storage rot of ginger (Zingiber officinale) by
Penicillium brevicompactum. J Food Protect 2005;68:
607609.
19. Bhattarai S, Tran VH, Duke CC. The stability of gingerol
and shogaol in aqueous solutions. J Pharm Sci
2001;90:16581664.
20. Guh J-H, Ko F-N, Jong T-T, Teng C-M. Antiplatelet effect
of gingerol isolated from Zingiber officinale. J Pharm
Pharmacol 1995;47:329332.
21. Lumb AB. Effect of dried ginger on human platelet
function. Thromb Haemost 1994;71:110111.
22. Bordia A, Verma SK, Srivastava KC. Effect of ginger
(Zingiber officinale Rosc.) and fenugreek (Trigonella foe-
numgraecum L.) on blood lipids, blood sugar and platelet
aggregation in patients with coronary artery disease. Pros-
taglandins Leukot Essent Fatty Acids 1997;56:379384.

23. Srivastava KC. Aqueous extracts of onion, garlic and
ginger inhibit platelet aggregation and alter arachidonic
acid metabolism. Biomed Biochim Acta 1984;43:S335
S346.
24. Dedov VN, Tran VH, Duke CC, Connor M, Christie MJ,
Mandadi S, Roufogalis BD. Gingerols: a novel class of
vanilloid receptor (VR1) agonists. Br J Pharmacol 2002;
137:793798.
25. Abdel-Aziz H, Windeck T, Ploch M, Verspohl EJ. Mode of
action of gingerols and s on 5-HT3 receptors: binding
studies, cation uptake by the receptor channel and con-
traction of isolated guinea-pig ileum. Eur J Pharmacol
2005;530:136143.
26. Nakazawa T, Ohsawa K. Metabolism of [6]-gingerol in
rats. Life Sci 2002;70:21652175.
27. Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis
BD, Duke CC, et al. Effect of ginkgo and ginger on the
pharmacokinetics and pharmacodynamics of warfarin
in healthy subjects. Br J Clin Pharmacol 2005;59:425
432.
28. Druth P, Brosi E, Fux R, Monke K, Gleiter CH. Ginger-
associated overanticoagulation by phenprocoumon.
Ann Pharmacother 2004;38:257260.
68 GINGER
29. Futrell JM, Rietschel RL. Spice allergy evaluated by
results of patch tests. Cutis 1993;52:288290.
30. Boone SA, Shields KM. Treating pregnancy-related nausea
and vomiting with ginger. Ann Pharmacother 2005;39:
17101713.
31. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea
and vomiting in pregnancy: randomized, double-masked,
placebo-controlled trial. Obstet Gynecol 2001;97:
577582.
32. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger
treatment of hyperemesis gravidarum. Eur J Obstet
Gynecol Reprod Biol 1991;38:1924.
33. Saha S, Smith RM, Lenz E, Wilson ID. Analysis of a ginger
extract by high-performance liquid chromatography
coupled to nuclear magnetic resonance spectroscopy using
superheated deuterium oxide as the mobile phase. J Chro-
matogr A 2003:991:143150.
34. Jiang H, Solyom AM, Timmermann BN, Gang DR. Char-
acterization of gingerol-related compounds in ginger
rhizome (Zingiber officinale Rosc.) by high-performance
liquid chromatography/electrospray ionization mass
spectrometry. Rapid Commun Mass Spectrom 2005;19:
29572964.
487